Hypertension (HT) is a leading risk factor for brain injury. Endothelial dysfunction can be observed in HT and may result in blood-brain barrier (BBB) impairment, which leads to neuroinflammation. We aimed to assess the contribution of brain endothelial dysfunction to HT-induced brain injury in mice. We induced the loss of NEMO, the essential modulator of nuclear factor-κB, in brain endothelial cells (NemobeKO). Control mice received tamoxifen (NemoFl). HT was induced by chronic infusion of angiotensin II and nitric oxide synthase inhibitor in the drinking water for 28 days. After 7 days, HT mice received additional subcutaneous injections of angiotensin II. Neurological signs were aggravated in NemobeKO/HT compared to NemoFl/HT. HT increased hypoxic areas in NemoFl and NemobeKO. Among NemobeKO, those with neurological signs had larger areas of hypoxia. Microvascular rarefaction occurred in NemobeKO mice and was exacerbated in the striatum. HT increased IgG extravasation in the striatum of NemoFl mice. Similarly, HT increased microglia numbers and astrocytic reactivity in NemoFl mice. In NemobeKO mice, an even stronger BBB impairment, increase in the number of microglia and astrocytic reactivity was detected and all parameters were further exacerbated with HT. Taken together, Nemo deletion in brain endothelial cells exacerbated HT-induced neurological signs, brain hypoxia, and microvascular rarefaction. This suggests that brain endothelial cell dysfunction, at least partially, plays a role in HT-induced brain injury. Further studies are needed to better characterize the cognitive outcome in this model and to pinpoint which factors are crucial to determine who develops neurological sequelae after HT.